Kessler Foundation Research Center

West Orange, NJ, United States

Kessler Foundation Research Center

West Orange, NJ, United States

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Rocca M.A.,Vita-Salute San Raffaele University | Rocca M.A.,San Raffaele Scientific Institute | Amato M.P.,University of Florence | De Stefano N.,University of Siena | And 8 more authors.
The Lancet Neurology | Year: 2015

In patients with multiple sclerosis (MS), grey matter damage is widespread and might underlie many of the clinical symptoms, especially cognitive impairment. This relation between grey matter damage and cognitive impairment has been lent support by findings from clinical and MRI studies. However, many aspects of cognitive impairment in patients with MS still need to be characterised. Standardised neuropsychological tests that are easy to administer and sensitive to disease-related abnormalities are needed to gain a better understanding of the factors affecting cognitive performance in patients with MS than exists at present. Imaging measures of the grey matter are necessary, but not sufficient to fully characterise cognitive decline in MS. Imaging measures of both lesioned and normal-appearing white matter lend support to the hypothesis of the existence of an underlying disconnection syndrome that causes clinical symptoms to trigger. Findings on cortical reorganisation support the contribution of brain plasticity and cognitive reserve in limiting cognitive deficits. The development of clinical and imaging biomarkers that can monitor disease development and treatment response is crucial to allow early identification of patients with MS who are at risk of cognitive impairment. © 2015 Elsevier Ltd.


Goedert K.M.,Seton Hall University | Boston R.C.,University of Pennsylvania | Barrett A.M.,Kessler Foundation Research Center
Frontiers in Human Neuroscience | Year: 2013

Valid research on neglect rehabilitation demands a statistical approach commensurate with the characteristics of neglect rehabilitation data: neglect arises from impairment in distinct brain networks leading to large between-subject variability in baseline symptoms and recovery trajectories. Studies enrolling medically ill, disabled patients, may suffer from missing, unbalanced data, and small sample sizes. Finally, assessment of rehabilitation requires a description of continuous recovery trajectories. Unfortunately, the statistical method currently employed in most studies of neglect treatment [repeated measures analysis of variance (ANOVA), rANOVA] does not well-address these issues. Here we review an alternative, mixed linear modeling (MLM), that is more appropriate for assessing change over time. MLM better accounts for between-subject heterogeneity in baseline neglect severity and in recovery trajectory. MLM does not require complete or balanced data, nor does it make strict assumptions regarding the data structure. Furthermore, because MLM better models between-subject heterogeneity it often results in increased power to observe treatment effects with smaller samples. After reviewing current practices in the field, and the assumptions of rANOVA, we provide an introduction to MLM. We review its assumptions, uses, advantages, and disadvantages. Using real and simulated data, we illustrate how MLM may improve the ability to detect effects of treatment over ANOVA, particularly with the small samples typical of neglect research. Furthermore, our simulation analyses result in recommendations for the design of future rehabilitation studies. Because between-subject heterogeneity is one important reason why studies of neglect treatments often yield conflicting results, employing statistical procedures that model this heterogeneity more accurately will increase the efficiency of our efforts to find treatments to improve the lives of individuals with neglect. © 2013 Goedert,Bostonand Barrett.


Whyte J.,Moss Rehabilitation Research Institute | Barrett A.M.,Kessler Foundation Research Center | Barrett A.M.,Rutgers University
Archives of Physical Medicine and Rehabilitation | Year: 2012

Translational research refers to the development of new scientific discoveries into evidence-based treatments for human diseases and conditions. This developmental process requires that a number of scientific, as well as social and psychological obstacles, be overcome during a sequence of research stages that address different goals. Rehabilitation, like other biomedical disciplines, requires this kind of developmental process. For a variety of reasons, however, development of rehabilitation treatments is less linear than the familiar phases of pharmaceutical research. In addition, research on treatments intended to address impairments (body structure/function, in terms of the International Classification of Functioning, Disability and Health), faces the challenge of determining the likely impact of an impairment-level treatment on the multifaceted activities and aspects of participation that are the typical goals of rehabilitation treatments. This article describes the application of treatment theory and enablement theory to the development of new impairment-based treatments, and examines similarities and differences between the developmental sequence needed for rehabilitation treatment research versus pharmaceutical research in other areas of medicine. © 2012 American Congress of Rehabilitation Medicine.


Sumowski J.F.,Kessler Foundation Research Center | Wylie G.R.,Kessler Foundation Research Center | Chiaravalloti N.,Kessler Foundation Research Center | Deluca J.,Kessler Foundation Research Center
Neurology | Year: 2010

Objective: Learning and memory impairments are prevalent among persons with multiple sclerosis (MS); however, such deficits are only weakly associated with MS disease severity (brain atrophy). The cognitive reserve hypothesis states that greater lifetime intellectual enrichment lessens the negative impact of brain disease on cognition, thereby helping to explain the incomplete relationship between brain disease and cognitive status in neurologic populations. The literature on cognitive reserve has focused mainly on Alzheimer disease. The current research examines whether greater intellectual enrichment lessens the negative effect of brain atrophy on learning and memory in patients with MS. Methods: Forty-four persons with MS completed neuropsychological measures of verbal learning and memory, and a vocabulary-based estimate of lifetime intellectual enrichment. Brain atrophy was estimated with third ventricle width measured from 3-T magnetization-prepared rapid gradient echo MRIs. Hierarchical regression was used to predict learning and memory with brain atrophy, intellectual enrichment, and the interaction between brain atrophy and intellectual enrichment. Results: Brain atrophy predicted worse learning and memory, and intellectual enrichment predicted better learning; however, these effects were moderated by interactions between brain atrophy and intellectual enrichment. Specifically, higher intellectual enrichment lessened the negative impact of brain atrophy on both learning and memory. Conclusion: These findings help to explain the incomplete relationship between multiple sclerosis disease severity and cognition, as the effect of disease on cognition is attenuated among patients with higher intellectual enrichment. As such, intellectual enrichment is supported as a protective factor against disease-related cognitive impairment in persons with multiple sclerosis. Copyright © 2010 by AAN Enterprises, Inc.


Sumowski J.F.,Kessler Foundation Research Center | Leavitt V.M.,Kessler Foundation Research Center
Multiple Sclerosis Journal | Year: 2013

Cognitive impairment is common among persons with multiple sclerosis (MS), but some patients are able to withstand considerable disease burden (e.g. white matter lesions, cerebral atrophy) without cognitive impairment (cognitive inefficiency, memory decline). What protects these patients from cognitive impairment? We review the literature on cognitive reserve in MS, which shows that heritable (larger maximal lifetime brain growth) and environmental (greater intellectual enrichment) factors attenuate the negative effect of disease burden on cognitive status. That is, persons with larger maximal lifetime brain growth, greater vocabulary knowledge, and/or greater early life participation in cognitive leisure activities (e.g. reading, hobbies) are better able to cope with MS disease without cognitive impairment. We review evidence that benefits of intellectual enrichment on cognitive status may stem from more efficient patterns of brain function. We discuss clinical implications and highlight important unanswered questions for future research on reserve against cognitive impairment in MS. © The Author(s) 2013.


Chiaravalloti N.D.,Kessler Foundation Research Center | Stojanovic-Radic J.,Kessler Foundation Research Center | Deluca J.,Kessler Foundation Research Center
Journal of Clinical and Experimental Neuropsychology | Year: 2013

The most common cognitive impairments in multiple sclerosis (MS) have been documented in specific domains, including new learning and memory, working memory, and information processing speed. However, little attempt has been made to increase our understanding of their relationship to one another. While recent studies have shown that processing speed impacts new learning and memory abilities in MS, the role of working memory in this relationship has received less attention. The present study examines the relative contribution of impaired working memory versus processing speed in new learning and memory functions in MS. Participants consisted of 51 individuals with clinically definite MS. Participants completed two measures of processing speed, two measures of working memory, and two measures of episodic memory. Data were analyzed via correlational and multiple regression analysis. Results indicate that the variance in new learning abilities in this sample was primarily associated with processing speed, with working memory exerting much less of an influence. Results are discussed in terms of the role of cognitive rehabilitation of new learning and memory abilities in persons with MS. © 2013 Copyright Taylor and Francis Group, LLC.


Rajagopalan V.,Cleveland Clinic | Rajagopalan V.,Kessler Foundation Research Center | Yue G.H.,Kessler Foundation Research Center | Pioro E.P.,Cleveland Clinic
Journal of Magnetic Resonance Imaging | Year: 2014

Purpose To study whether inconsistent findings in voxel-based morphometry (VBM) in amyotrophic lateral sclerosis (ALS) brain are due to use of different data preprocessing and statistical methods in two software packages. Materials and Methods T1-weighted magnetic resonance imaging (MRI) was obtained during routine clinical imaging at 1.5T in ALS patients with frontotemporal dementia (ALS-FTD) (n=18) and in unaffected neurologic controls (n=15). Gray matter (GM) VBM analysis was carried out using FMRIB software library (FSL) 4.1.5 and statistical parametric mapping 8 (SPM8). Comparison of processing steps segmentation, registration, and statistical methods (nonparametric vs. parametric) between the two softwares was performed by subjecting the same dataset through standard VBM processing pipelines. Results GM volume was significantly (P<0.05) reduced in motor and extramotor regions of ALS-FTD when compared to controls. Percentage of atrophied GM voxels in the entire brain that reached statistical significance using FSL was 22.52% compared to 0.81% in SPM. Similarly, 0.81% (3308 voxels) reached statistical significance using nonparametric statistics when compared to parametric statistics (0.50%, 2056 voxels). Conclusion The differences in GM volume atrophy measures found by FSL and SPM analytic methods indicate that variable results in previous VBM studies may arise from differences in their image processing algorithms and statistical models. © 2013 Wiley Periodicals, Inc.


Arnett P.A.,Pennsylvania State University | Strober L.B.,Kessler Foundation Research Center
Expert Review of Neurotherapeutics | Year: 2011

Multiple sclerosis (MS) is the most common nontraumatic neurological condition of early and middle adulthood. Cognitive and neurobehavioral problems associated with this disorder are common. Approximately 50% of MS patients experience lifetime clinical depression, and at least 50% will experience significant cognitive difficulties. Fatigue is also extremely common and disabling in MS and appears to be associated with sleep problems and primary neurological features, in addition to secondary factors, including depression and pain. Quality of life is affected in MS by all of these factors and is an especially salient issue given that patients often live for many years following diagnosis. In this article, we explore the literature on cognitive and neurobehavioral features in MS, provide a commentary on the state of the literature and make suggestions for research directions over the next 5 years that would move the field forward significantly. © 2011 Expert Reviews Ltd.


Leavitt V.M.,Kessler Foundation Research Center | Sumowski J.F.,Kessler Foundation Research Center | Chiaravalloti N.,Kessler Foundation Research Center | DeLuca J.,Kessler Foundation Research Center
Neurology | Year: 2012

Objective: Patients with multiple sclerosis (MS) have more clinical exacerbations and T2 lesion activity during warmer weather. The current study is the first to investigate whether outdoor temperature is related to cognitive status across patients with MS (cross-sectional analysis), and whether cognitive status fluctuates with changes in outdoor temperature within patients with MS (longitudinal analysis). Methods: For the cross-sectional analysis, 40 patients with MS and 40 healthy control (HC) subjects were recruited throughout the calendar year. Cognitive status (processing speed, memory) and outdoor temperature were recorded for the day of testing. We calculated partial correlations between cognitive status and temperature for patients with MS and HCs, controlling for demographic and disease variables. For the longitudinal analysis, cognitive status and outdoor temperature were recorded at baseline and 6-month follow-up in a separate sample of 45 patients with MS. We calculated the partial correlation between temperature and cognitive status at follow-up, controlling for baseline temperature and cognitive status (i.e., whether temperature changes are related to cognitive changes within patients with MS). Results: Cross-sectionally, warmer temperature was related to worse cognitive status in patients with MS (rp = -0.45, p = 0.006), not in HCs (rp = 0.00, p = 0.984). Longitudinally, increased outdoor temperature from baseline to follow-up was related to a decline in cognitive status within patients with MS (rp=-0.39, p = 0.010). Conclusions: Cognitive status in patients with MS is worse on warmer days, consistent with a previously established link between heat and lesion activity. Our findings have implications for clinical trial planning, treatment, and lifestyle decisions. We discuss cognitive status as a potential marker of quiescent exacerbations. Copyright © 2012 by AAN Enterprises, Inc.


Chiaravalloti N.D.,Kessler Foundation Research Center | Wylie G.,Kessler Foundation Research Center | Leavitt V.,Kessler Foundation Research Center | DeLuca J.,Kessler Foundation Research Center
Journal of Neurology | Year: 2012

Deficits in new learning and memory are common in persons with multiple sclerosis (MS), though few studies have examined the efficacy of memory retraining in MS. Previous research from our laboratory has demonstrated that the modified Story Memory Technique (mSMT) significantly improves new learning and memory in MS. The present double-blind, placebo-controlled, randomized clinical trial was designed to examine changes in cerebral activation following mSMT treatment. Sixteen individuals with clinically definite MS were randomly assigned to treatment (n = 8) or placebo-control (n = 8) groups, matched for age, education, and disease characteristics. Baseline and follow-up fMRI was collected during performance of learning and memory tasks. No baseline activation differences on fMRI were seen between groups. After treatment, greater activation was evident in the treatment group during performance of a memory task within a widespread cortical network involving frontal, parietal, precuneus, and parahippocampal regions. All participants in the treatment group showed increased activation in frontal and temporal regions in particular. In contrast, the control group showed no significant changes in cerebral activation at follow-up. A significant association was found between increased activation in the right middle frontal gyrus and improved memory performance post-treatment. The increased activation seen likely reflects increased use of strategies taught during treatment when learning new information. This study is the first to demonstrate a significant change in cerebral activation resulting from a behavioral memory intervention in an MS sample. Behavioral interventions can show significant changes in the brain, validating clinical utility. © Springer-Verlag 2011.

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